Mechanotransduction of axonal growth

Axonal growth has attracted considerable interest in the last decades. Historically, axon outgrowth was understood to be exclusively governed by the growth cone and its capability of influencing axonal elongation in response to chemical cues. However, recent discoveries suggest that axonal growth, elongation and maturation are also regulated by mechanical forces, being the process named “stretch growth”. Considering that mechanical force is also known to influence the nervous system development and any stage of neural development, scientists are spending many efforts to elucidate the signaling cascade of the mechanotransduction of axonal growth. Here, to study the mechanisms that underlie stretch growth, two methods have been developed to stretch axons: the magnetically-actuated microposts and the magnetic nanoparticles. Both technologies are biologically compliant and allow living cell studies (both “molecule by molecule” high throughput approaches). Mechanical forces generated by both technologies strongly increase axonal elongation and sprouting. However, "What is behind the mechanotransduction of axonal growth?" is still an open question. The hypothesis that emerges from this study is that stretch growth influences microtubule dynamics and microtubules, in turn, orchestrate a local "cross-talk" between local mechanisms, i.e. axonal transport and local translation, in response to mechanical tension. This opens many interesting scenarios not only for understanding the mechanisms that underlie the development of the central nervous system but also for developing novel therapeutic methods for the regeneration of injured or sick neurons.